Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Cisplatin and Capecitabine for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
Primary Purpose
Esophageal Squamous Cell Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
nab-paclitaxel
Cisplatin
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologic pathological or cytological diagnosis of squamous cell carcinoma of esophagus
- Age ranges from 18 to 70 years
- Patients must not have received any prior anticancer therapy
- Preoperative stage cT2N+M0, cT3-4aN0/N+M0 thoracic esophageal squamous cell carcinoma evaluated by MDT consultation based on imaging examinations
- Eastern cooperative oncology group (ECOG) performance status of 0 to 1
- Signed informed consent document on file
- Females with childbearing potential must have a negative serum pregnancy
- Adequate organ function to receive esophagectomy including the following:
Bone marrow: absolute white blood cells count ≥3.0×10^9/L, absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥100×10^9/L, haemoglobin ≥90g/L; Hepatic: total bilirubin ≤1.5 times upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) ≤2.5 times ULN; Renal: calculated creatinine clearance rate≥80ml/min
- For childbearing potential males and females, who have agreed with contraception from start of investigational drug administration to 6 months after last dose of investigational drug
- Patients who have no contraindication of nab-paclitaxel, cisplatin or capecitabine
Exclusion Criteria:
- Patients who may develop tracheoesophageal fistula or aortoesophageal fistula
- Patients who have received allogeneic organ or stem cell transplants
- Patients with uncontrolled diabetes mellitus, any serious or unstable medical condition or mental illness
- Patients with preexisting or a history of ≥ Grade II peripheral neuropathy
- Pregnant or breast feeding
- Patients who take part in clinical trials of other drugs or biological therapy within 4 weeks before enrollment
- Prior invasive malignancy in 5 years (except for curable carcinoma in situ of cervix and non-melanoma skin cancer)
- Patients with digestive tract obstruction or metabolic dysfunction which may influence oral absorption of capecitabine
- Patients with supraclavicular lymph node metastasis, celiac lymph node metastasis except for pericardial and left gastric lymph node metastasis
- Patients with evidence of distant metastases
Sites / Locations
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Neoadjuvant chemotherapy group
Arm Description
Total 6 perioperative chemotherapy composed of nab-paclitaxel, cisplatin and capecitabine every 21 days
Outcomes
Primary Outcome Measures
Pathological complete response (pCR) rate
No cancer cells in primary tumor and all lymph nodes resected are observed by pathologists
Secondary Outcome Measures
Objective Response Rate (ORR)
Objective response rate is defined as the rate of patients with at least a 30% decrease in the sum of the LD (longest diameter) of target lesions, which include complete response (CR) or partial response (PR)
R0 resection rate
The ratio of the patients with surgical R0 resection over the of patients who receive surgery
Major Pathological Response (MPR) rate
MPR is defined as 10% or fewer viable cancer cells in the hematoxylin and eosin (H&E)-stained slides from the resected tumor following neoadjuvant treatment
Overall survival (OS)
Time from enrollment to death
Disease free survival (DFS)
From the day of surgery with R0 resection to recurrence or death of any reasons
Progression-free survival (PFS)
number of participant with disease progression
Recurrence rate
number of participant with disease recurrence
Treatment-emergent adverse events
From the day of neoadjuvant therapy to 30 days after surgery or within 90 days after last neoadjuvant treatment. To evaluate the incidence of TEAE, rate of grade 3 and 4 TEAE (CTCAE 5.0), rate of surgery delay over 30 days and/or inoperable patients
Surgical complications
Full Information
NCT ID
NCT04390958
First Posted
May 13, 2020
Last Updated
March 13, 2022
Sponsor
Chinese Academy of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT04390958
Brief Title
Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Cisplatin and Capecitabine for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
Official Title
Phase II Study of Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Cisplatin and Capecitabine for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 15, 2020 (Actual)
Primary Completion Date
June 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Surgical resection is currently the major treatment for esophageal carcinoma while disease progression still occurred in most cases within 3 years. The rate of local recurrence and distant metastases could reach nearly 40% to 60%. The neoadjuvant chemotherapy could significantly improve resection rate and overall survival after surgery. Squamous cell carcinoma is the most common histology in Asia. JCOG9907 trial performed in Japan confirmed that compared to surgery plus adjuvant chemotherapy, the combination of neoadjuvant chemotherapy and surgery could further prolong overall survival. The regimen of cisplatin and fluorouracil is a classic effective option in combination therapy for esophageal carcinoma. Nanoparticle albumin-bound (nab)-paclitaxel is a novel taxane and has better efficacy in esophageal carcinoma treatment. We try to evaluate the efficacy and safety of neoadjuvant chemotherapy with nab-paclitaxel plus cisplatin and capecitabine for locally advanced thoracic esophageal squamous cell carcinoma patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Neoadjuvant chemotherapy group
Arm Type
Experimental
Arm Description
Total 6 perioperative chemotherapy composed of nab-paclitaxel, cisplatin and capecitabine every 21 days
Intervention Type
Drug
Intervention Name(s)
nab-paclitaxel
Intervention Description
125mg/m2 ivgtt d1、d8
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
60mg/m2 ivgtt d1 or d1-2
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
1750mg/m2 po bid d1-14
Primary Outcome Measure Information:
Title
Pathological complete response (pCR) rate
Description
No cancer cells in primary tumor and all lymph nodes resected are observed by pathologists
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Objective response rate is defined as the rate of patients with at least a 30% decrease in the sum of the LD (longest diameter) of target lesions, which include complete response (CR) or partial response (PR)
Time Frame
2 year
Title
R0 resection rate
Description
The ratio of the patients with surgical R0 resection over the of patients who receive surgery
Time Frame
2 year
Title
Major Pathological Response (MPR) rate
Description
MPR is defined as 10% or fewer viable cancer cells in the hematoxylin and eosin (H&E)-stained slides from the resected tumor following neoadjuvant treatment
Time Frame
2 year
Title
Overall survival (OS)
Description
Time from enrollment to death
Time Frame
From date of enrollment until the date of death from any cause, assessed up to 24 months
Title
Disease free survival (DFS)
Description
From the day of surgery with R0 resection to recurrence or death of any reasons
Time Frame
From date of enrollment until the date of death or recurrence, assessed up to 24 months
Title
Progression-free survival (PFS)
Description
number of participant with disease progression
Time Frame
From date of enrolment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months
Title
Recurrence rate
Description
number of participant with disease recurrence
Time Frame
2 year
Title
Treatment-emergent adverse events
Description
From the day of neoadjuvant therapy to 30 days after surgery or within 90 days after last neoadjuvant treatment. To evaluate the incidence of TEAE, rate of grade 3 and 4 TEAE (CTCAE 5.0), rate of surgery delay over 30 days and/or inoperable patients
Time Frame
2 year
Title
Surgical complications
Time Frame
Within the first 90 days after the start of surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologic pathological or cytological diagnosis of squamous cell carcinoma of esophagus
Age ranges from 18 to 70 years
Patients must not have received any prior anticancer therapy
Preoperative stage cT2N+M0, cT3-4aN0/N+M0 thoracic esophageal squamous cell carcinoma evaluated by MDT consultation based on imaging examinations
Eastern cooperative oncology group (ECOG) performance status of 0 to 1
Signed informed consent document on file
Females with childbearing potential must have a negative serum pregnancy
Adequate organ function to receive esophagectomy including the following:
Bone marrow: absolute white blood cells count ≥3.0×10^9/L, absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥100×10^9/L, haemoglobin ≥90g/L; Hepatic: total bilirubin ≤1.5 times upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) ≤2.5 times ULN; Renal: calculated creatinine clearance rate≥80ml/min
For childbearing potential males and females, who have agreed with contraception from start of investigational drug administration to 6 months after last dose of investigational drug
Patients who have no contraindication of nab-paclitaxel, cisplatin or capecitabine
Exclusion Criteria:
Patients who may develop tracheoesophageal fistula or aortoesophageal fistula
Patients who have received allogeneic organ or stem cell transplants
Patients with uncontrolled diabetes mellitus, any serious or unstable medical condition or mental illness
Patients with preexisting or a history of ≥ Grade II peripheral neuropathy
Pregnant or breast feeding
Patients who take part in clinical trials of other drugs or biological therapy within 4 weeks before enrollment
Prior invasive malignancy in 5 years (except for curable carcinoma in situ of cervix and non-melanoma skin cancer)
Patients with digestive tract obstruction or metabolic dysfunction which may influence oral absorption of capecitabine
Patients with supraclavicular lymph node metastasis, celiac lymph node metastasis except for pericardial and left gastric lymph node metastasis
Patients with evidence of distant metastases
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aiping Zhou, MD
Phone
8613691161998
Email
Zhouap1825@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shugeng Gao, MD
Organizational Affiliation
Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhou Aiping
Phone
+86 13691161998
Email
zhouap1825@126.com
12. IPD Sharing Statement
Learn more about this trial
Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Cisplatin and Capecitabine for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
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